Cargando…
Solution Structure of SpoIVB Reveals Mechanism of PDZ Domain-Regulated Protease Activity
Intramembrane proteases hydrolyze peptide bonds within the cell membrane as the decision-making step of various signaling pathways. Sporulation factor IV B protease (SpoIVB) and C-terminal processing proteases B (CtpB) play central roles in cellular differentiation via regulated intramembrane proteo...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6581720/ https://www.ncbi.nlm.nih.gov/pubmed/31244791 http://dx.doi.org/10.3389/fmicb.2019.01232 |
_version_ | 1783428197778456576 |
---|---|
author | Xie, Xie Guo, Nannan Xue, Guangpu Xie, Daoqing Yuan, Cai Harrison, Joshua Li, Jinyu Jiang, Longguang Huang, Mingdong |
author_facet | Xie, Xie Guo, Nannan Xue, Guangpu Xie, Daoqing Yuan, Cai Harrison, Joshua Li, Jinyu Jiang, Longguang Huang, Mingdong |
author_sort | Xie, Xie |
collection | PubMed |
description | Intramembrane proteases hydrolyze peptide bonds within the cell membrane as the decision-making step of various signaling pathways. Sporulation factor IV B protease (SpoIVB) and C-terminal processing proteases B (CtpB) play central roles in cellular differentiation via regulated intramembrane proteolysis (RIP) process which activates pro-σ(K) processing at the σ(K) checkpoint during spore formation. SpoIVB joins CtpB in belonging to the widespread family of PDZ-proteases, but much remains unclear about the molecular mechanisms and structure of SpoIVB. In this study, we expressed inactive SpoIVB (SpoIVB(S378A)) fused with maltose binding protein (MBP)-tag and obtained the solution structure of SpoIVB(S378A) from its small angle X-ray scattering (SAXS) data. The fusion protein is more soluble, stable, and yields higher expression compared to SpoIVB without the tag. MBP-tag not only facilitates modeling of the structure in the SAXS envelope but also evaluates reliability of the model. The solution structure of SpoIVB(S378A) fits closely with the experimental scattering data (χ(2)= 1.76). Comparing the conformations of PDZ-proteases indicates that SpoIVB adopts a PDZ-protease pattern similar to the high temperature requirement A proteases (HtrAs) rather than CtpB. We not only propose that SpoIVB uses a more direct and simple way to cleave the substrates than that of CtpB, but also that they work together as signal amplifiers to activate downstream proteins in the RIP pathway. |
format | Online Article Text |
id | pubmed-6581720 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-65817202019-06-26 Solution Structure of SpoIVB Reveals Mechanism of PDZ Domain-Regulated Protease Activity Xie, Xie Guo, Nannan Xue, Guangpu Xie, Daoqing Yuan, Cai Harrison, Joshua Li, Jinyu Jiang, Longguang Huang, Mingdong Front Microbiol Microbiology Intramembrane proteases hydrolyze peptide bonds within the cell membrane as the decision-making step of various signaling pathways. Sporulation factor IV B protease (SpoIVB) and C-terminal processing proteases B (CtpB) play central roles in cellular differentiation via regulated intramembrane proteolysis (RIP) process which activates pro-σ(K) processing at the σ(K) checkpoint during spore formation. SpoIVB joins CtpB in belonging to the widespread family of PDZ-proteases, but much remains unclear about the molecular mechanisms and structure of SpoIVB. In this study, we expressed inactive SpoIVB (SpoIVB(S378A)) fused with maltose binding protein (MBP)-tag and obtained the solution structure of SpoIVB(S378A) from its small angle X-ray scattering (SAXS) data. The fusion protein is more soluble, stable, and yields higher expression compared to SpoIVB without the tag. MBP-tag not only facilitates modeling of the structure in the SAXS envelope but also evaluates reliability of the model. The solution structure of SpoIVB(S378A) fits closely with the experimental scattering data (χ(2)= 1.76). Comparing the conformations of PDZ-proteases indicates that SpoIVB adopts a PDZ-protease pattern similar to the high temperature requirement A proteases (HtrAs) rather than CtpB. We not only propose that SpoIVB uses a more direct and simple way to cleave the substrates than that of CtpB, but also that they work together as signal amplifiers to activate downstream proteins in the RIP pathway. Frontiers Media S.A. 2019-06-12 /pmc/articles/PMC6581720/ /pubmed/31244791 http://dx.doi.org/10.3389/fmicb.2019.01232 Text en Copyright © 2019 Xie, Guo, Xue, Xie, Yuan, Harrison, Li, Jiang and Huang. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Microbiology Xie, Xie Guo, Nannan Xue, Guangpu Xie, Daoqing Yuan, Cai Harrison, Joshua Li, Jinyu Jiang, Longguang Huang, Mingdong Solution Structure of SpoIVB Reveals Mechanism of PDZ Domain-Regulated Protease Activity |
title | Solution Structure of SpoIVB Reveals Mechanism of PDZ Domain-Regulated Protease Activity |
title_full | Solution Structure of SpoIVB Reveals Mechanism of PDZ Domain-Regulated Protease Activity |
title_fullStr | Solution Structure of SpoIVB Reveals Mechanism of PDZ Domain-Regulated Protease Activity |
title_full_unstemmed | Solution Structure of SpoIVB Reveals Mechanism of PDZ Domain-Regulated Protease Activity |
title_short | Solution Structure of SpoIVB Reveals Mechanism of PDZ Domain-Regulated Protease Activity |
title_sort | solution structure of spoivb reveals mechanism of pdz domain-regulated protease activity |
topic | Microbiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6581720/ https://www.ncbi.nlm.nih.gov/pubmed/31244791 http://dx.doi.org/10.3389/fmicb.2019.01232 |
work_keys_str_mv | AT xiexie solutionstructureofspoivbrevealsmechanismofpdzdomainregulatedproteaseactivity AT guonannan solutionstructureofspoivbrevealsmechanismofpdzdomainregulatedproteaseactivity AT xueguangpu solutionstructureofspoivbrevealsmechanismofpdzdomainregulatedproteaseactivity AT xiedaoqing solutionstructureofspoivbrevealsmechanismofpdzdomainregulatedproteaseactivity AT yuancai solutionstructureofspoivbrevealsmechanismofpdzdomainregulatedproteaseactivity AT harrisonjoshua solutionstructureofspoivbrevealsmechanismofpdzdomainregulatedproteaseactivity AT lijinyu solutionstructureofspoivbrevealsmechanismofpdzdomainregulatedproteaseactivity AT jianglongguang solutionstructureofspoivbrevealsmechanismofpdzdomainregulatedproteaseactivity AT huangmingdong solutionstructureofspoivbrevealsmechanismofpdzdomainregulatedproteaseactivity |